As shown in Scheme 2.8, the racemic starting ester (A/B) is hydrolyzed to give
alcohols (P/Q) in an organic medium containing a minimum amount of water,
which in turn, by the action of the same lipase, are re-esterified with cyclohexanoic
acid present in the mixture. Thus, the alcohol moiety of the substrate has to enter the
active site of the lipase twice during the course of its transformation into the final
product ester (R/S). An apparent selectivity of E tot ¼ 400 was achieved in this way,
whereas the corresponding isolated single-step resolutions of this process were
E 1 ¼ 8 for the hydrolysis of acetate A/B, and E 2 ¼ 97 for the esterification of
alcohol P/Q with cyclohexanoic acid.
Deracemization
Despite its widespread use, kinetic resolution has several disadvantages, particularly on an industrial scale. After all, an ideal process should lead to a single
enantiomeric product in 100% chemical yield. The drawbacks of kinetic resolution
are as follows:
• The theoretical yield of each enantiomer is limited to 50%. Furthermore, in
general only one stereoisomer is desired and there is little or no use for the other.
• Separation of the product from the remaining substrate may be laborious, in
particular when simple extraction or distillation fails [63].
• As explained above, the optical purity of substrate and/or product is often less
than perfect for kinetic reasons.
To overcome these disadvantages by avoiding the occurrence of the undesired
‘wrong’ enantiomer, several strategies are possible [64, 65]. All of these processes
which lead to the formation of a single stereoisomeric product from a racemate are
called ‘deracemizations’ [66–68].
O
O
O
O
O
O
O
O
OH
HO
(Esterification)
(Hydrolysis)
conditions: water-saturated hexane, cyclohexane carboxylic
acid,
Mucor sp. lipase
+ H 2 O
k 1
k 3
k 2
k 4
A
B
P
Q
R
S
CO 2 H
+
k 1 / k 3 = 8
k 2 / k 4 = 97
Scheme 2.8 Sequential enzymatic kinetic resolution of monofunctional substrate via concurrent
hydrolysis-esterification in aqueous-organic solvent
46
2 Biocatalytic Applications
alcohols (P/Q) in an organic medium containing a minimum amount of water,
which in turn, by the action of the same lipase, are re-esterified with cyclohexanoic
acid present in the mixture. Thus, the alcohol moiety of the substrate has to enter the
active site of the lipase twice during the course of its transformation into the final
product ester (R/S). An apparent selectivity of E tot ¼ 400 was achieved in this way,
whereas the corresponding isolated single-step resolutions of this process were
E 1 ¼ 8 for the hydrolysis of acetate A/B, and E 2 ¼ 97 for the esterification of
alcohol P/Q with cyclohexanoic acid.
Deracemization
Despite its widespread use, kinetic resolution has several disadvantages, particularly on an industrial scale. After all, an ideal process should lead to a single
enantiomeric product in 100% chemical yield. The drawbacks of kinetic resolution
are as follows:
• The theoretical yield of each enantiomer is limited to 50%. Furthermore, in
general only one stereoisomer is desired and there is little or no use for the other.
• Separation of the product from the remaining substrate may be laborious, in
particular when simple extraction or distillation fails [63].
• As explained above, the optical purity of substrate and/or product is often less
than perfect for kinetic reasons.
To overcome these disadvantages by avoiding the occurrence of the undesired
‘wrong’ enantiomer, several strategies are possible [64, 65]. All of these processes
which lead to the formation of a single stereoisomeric product from a racemate are
called ‘deracemizations’ [66–68].
O
O
O
O
O
O
O
O
OH
HO
(Esterification)
(Hydrolysis)
conditions: water-saturated hexane, cyclohexane carboxylic
acid,
Mucor sp. lipase
+ H 2 O
k 1
k 3
k 2
k 4
A
B
P
Q
R
S
CO 2 H
+
k 1 / k 3 = 8
k 2 / k 4 = 97
Scheme 2.8 Sequential enzymatic kinetic resolution of monofunctional substrate via concurrent
hydrolysis-esterification in aqueous-organic solvent
46
2 Biocatalytic Applications